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The Thyroid Gland
Learning Objectives
Be able to answer “What is the thyroid gland?” Understand the form and function of Thyroid
hormone Understand the importance of Iodine
Become familiar with thyroid regulatory mechanisms
Understand the role of the thyroid in maintaining metabolic balance
Get a feeling for how thyroid dysfunction could affect a patient.
Hormones Regulate Energy Useage
Where does energy go in the body? Digestion & Absorption
Pancreas: Insulin & Glucagon
Physical activity Adrenal Glands: Adrenaline, Cortisol
Basal Metabolism Thyroid: Thyroxine
Basal Metabolism
Energy required just to stay alive Maintain cellular respiration Allow vital organs to function
Influences on basal metabolism Lean Body Mass Age Growth requirements Thyroid Hormone
Meet the Thyroid The Thyroid is a large, bi-lobed gland,
positioned in the neck.
20-60 grams in an adult You can feel your thyroid: place a finger to
either side of the neck, below the thyroid cartilage (the “Adam’s Apple”), and swallow. The spongy, soft tissue you can feel move beneath the skin is your thyroid gland
Where does it come from?
In the human embryo, tissue that becomes the thyroid starts in the same place as the tongue.
It then migrates distally as fetal development continues, ultimately reaching its adult position.
Rare but interesting result: misplaced thyroid tissue may occur along the path that the thyroid travels, called the Thyroglossal Duct. Important in ruling out thyroid cancer.
Quick Histo Review
What does it do?
Produces and releases Thyroxine (T4), the thyroid hormone.
Allows for maintenance of basal metabolic rate
Thyroid
Metabolically active cells
Who needs a thyroid?
Everyone! In infants, a lack of thyroid hormone
will quickly lead to permanent developmental impairments.
In adults, lack of thyroid hormone is not as devastating, but still causes significant problems if untreated.
Thyroid Hormone
Thyroid hormone is the main product of the thyroid gland
It is produced by action of the follicular cells
It is synthesized extracellularly from protein, called colloid, stored in the follicles.
So, what IS thyroid Hormone?
Thyroxine, or T4, Starts its life as Tyrosine residues in a protein called Thyroglobulin, the main component of Colloid.
So, what IS thyroid Hormone?
Enzymes in the thyroid add Iodine to the Tyrosine residues, forming Diiodotyrosine
So, what IS thyroid Hormone?
Two of these residues are then joined together to form Thyroxine, or T4.
What’s the only part of that you need to care about?
Iodine! The thyroid needs a lot of it! Or at least 80 g per day. Despite the gland being ~0.05% of the body
weight, 30% of the body’s iodine is in the thyroid Why might this be significant?
A lack of iodine will affect the thyroid first Too much iodine will affect the thyroid first Radioactive iodine will concentrate in the thyroid,
which is exploited in medicine. Low doses: imaging High doses: destroy the thyroid
So we’ve made T4, what now? T4 is actually not very potent In order to be maximally effective, one Iodine has to
be removed to form Triiodothyronine, or T3 This conversion occurs systemically, by the action
of deiodonase I and II A third deiodonase
produces reverse T3,
which is inactive
What? Why?!
It’s all about regulation T4 has low activity, is present in high
concentration, is cleared slowly,and is heavily protein bound. It provides a reservoir for the rapid production of T3.
T3 has high activity, is present in low concentration, is cleared quickly, and is slightly less protein bound. This allows the body to quickly eliminate T3 if it’s had enough.
Thyroid function is under two regulatory systems
The Hypothalamus-Pituitary-Thyroid Axis: good for long-term maintenance
TRH TSH T4,T3+ +
--
Thyroid function is under two regulatory systems
Systemic Deiodonase Balance: good for maintaining fine control
-Cortisol
Other regulating factors
Release of TRH and activity of Deiodonase II are also under thermogenic control.
TSH, DI II
T4,T3
-+
How do T4&T3 work?
Unbound T4 and T3 enter cells by an uncertain mechanism – evidence of both diffusion and transporter-mediated cell entry.
Once inside, the hormones bind to Thyroid Response elements TREs associate with DNA and other proteins to form
regulatory complexes. If the TRE is binding hormone, then it forms a gene
promotor complex If the TRE is not binding hormone, it forms a gene
supressor complex
How do T4&T3 work?
Therefore, thyroid hormone both: Promotes the transcription of some genes Prevents the suppression of other genes
Get to how this affects metabolism already!!
OK! OK! Calm Down! Gene products promoted by hormone-bound TREs include: Increased transcription of RNA Polymerase I:
this leads to inceased production of ALL protein-coding mRNAs.
Protease concentrations and activities also increase: this leads to faster degredation of all cellular proteins.
In a hypertyroid state, the catabolic effect exceeds the anabolic effect
More Effects
Synthesis and activity of -adrenergic receptors increase Increases sensitivity of body to
Epinephrine and Norepinepherine Especially true in heart Leads to increased stroke volume and
speed
More effects
OF SPECIAL NOTE IN INFANTS! Thyroid hormone is VITAL
to the proper development of the nervous system
Induces myelination, axon growth, neurotransmitter production.
Infants with uncorrected hypothyroidism develop a syndrome of dwarfism and mental disability (previously termed ‘cretinism’).
So, knowing the effects… What would happen if there’s too LITTLE Thyroid
hormone? Less protein turnover = less need for energy, O2
Slower heart rate, slower breathing, loss of appetite combined with weight gain
Loss of Thermogenic control Low body temp, cold intolerance
Cells that turn over quickly, like skin and hair, can’t be replaced fast enough Thin, brittle skin; hair loss In women: irregular menstrual cycle
Blunting of sympathetic (fight/flight) response Fatigue, exercise intolerance Weak pulse, slow maximum heart rate
Nervous system involvement Poor memory, inability to concentrate Parasthesia, i.e. “pins and needles” Loss of hearing
SummarryTable 335-5 Signs and Symptoms of Hypothyroidism (Descending Order of Frequency)
Symptoms Tiredness, weakness Dry skin Feeling cold Hair loss Difficulty concentrating and poor memory Constipation Weight gain with poor appetite Dyspnea Hoarse voice Menorrhagia (later oligomenorrhea or amenorrhea) Paresthesia Impaired hearing
Signs Dry coarse skin; cool peripheral extremities Puffy face, hands, and feet (myxedema) Diffuse alopecia Bradycardia Peripheral edema Delayed tendon reflex relaxation Carpal tunnel syndrome Serous cavity effusions
Major causes?
Congenital Thyroid agenesis Failure to produce any of the hormones
necessary to ultimately make T3 Mutations in thyroid-binding proteins, thyroid
response elements, or transporters. Acquired
Autoimmune: body attacks own thyroid Infective: virus attacks thyroid Nutritional: Iodine deficiency Drug induced
How about Hyperthyroidism?
Protein turnover is too rapid, high O2 and metabolic demands Fast heart rate, fast breathing, loss of weight despite
ravenous appetite Ketotic state Muscle weakness (remember, cata > ana)
Loss of Thermogenic control Always generating too much heat; heat intolerance,
disproportionate sweating Exaggerated Sympathetic response
Hyperactivity, Irritability Bounding pulse, tachycardia, palpitations Tremor
Table 335-7 Signs and Symptoms of Thyrotoxicosis (Descending Order of Frequency)
Symptoms Signsa
Hyperactivity, irritability, dysphoria Heat intolerance and sweating Palpitations Fatigue and weakness Weight loss with increased appetite Diarrhea Polyuria Oligomenorrhea, loss of libido
Tachycardia; atrial fibrillation in the elderly Tremor Goiter Warm, moist skin Muscle weakness, proximal myopathy Lid retraction or lag Gynecomastia
Causes
Autoimmune: Grave’s Disease Body produces antibodies that mimic TSH
Neoplastic / Hyperplasic Primary goiter (Multinodular Goiter) Thyroid adenoma, other active endocrine
adenoma Nutritional
Too much iodine Consuming thyroid tissue as supplement
Drug induced
Anyone still paying attention?
Or are you all just feeling dragged along?
VISUAL METAPHOR TIME!
With the right amount of thyroid hormone:
If there’s too little…
If there’s too much…
Compare to too much HGH
Revisiting the LOs
What is the Thyroid Gland? A large, bi-lobed gland in the neck The endocrine gland in charge of
maintaining basal metabolism
Revisiting the LOs
Thyroid hormone You need iodine to make it Acts on all metabolically active tissue Stimulates protein synthesis and turnover
Iodine Need 80 g per day (150 g oral intake) Radioiodine can be used in thyroid
medicine
LOs, cont.
Thyroid regulation: H-P-T axis for slow regulation
Classic negative feedback setup Systemic Deiodonase activity for fast
LOs, cont.
Effects of thyroid abnormality Hypothyroid: weight gain, loss of energy,
cold intolerance, PERMANENT neural damage in infants.
Hyperthyroid: weight loss, hyperactivity, tachycardia, heat intolerance, muscle wasting
Aaaaaand…we’re done!